The purpose of this project is to gain further insight into the mechanisms of concentrative transport and the relationship of transepithelial transport to cellular accumulation of organic molecules in the mammalian renal tubule. The technique of section freeze-dry autoradiography devised in this laboratory will be extended to studies of the pathophysiology of experimental and clinical renal disease. At the physiologic level, experiments in animals are designed to further examine the effects of transport inhibitors and stimulators on the distribution of tritiated p-aminohippurate (PAH) and alpha- aminoisobutyric acid (AIB) in rat kidney slices. The direction of entry of these compounds will be determined by in vivo microperfusion of tubules and capillaries, and the cellular sites of accumulation of tritiated lysine and arginine will be determined in vivo. Pathophysiologic studies are designed to determine the effects of maleic acid, AIB, potassium dichromate, and mercuric chloride on concentrative transport of PAH-H3 and AIB-H3. Section freeze-dry autoradiography and a modified uptake technique will be used to examine tubular cell function in human renal biopsies in vitro and for viability testing of isolated perfused dog kidneys. These studies of concentrative transport by section freeze-dry autoradiography should not only increase our understanding of transport mechanisms, but may permit classification of human renal tubular dysfunction based on direct examination of cellular function.